SeattieSNPs is a joint program between the University of Washington (UW) and the Fred Hutchinson Cancer Research Center (FHCRC) focused on identifying, genotyping, and modeling the associations between single nucleotide polymorphisms (SNPs) in candidate genes and pathways that underlie inflammatory responses in humans. Inflammation is a basic physiologic response linked to a wide variety of common human disorders including asthma, chronic obstructive pulmonary disease, coronary artery disease and stroke, and markers of this response have been identified that sensitive predictors of human disease risk such as C-reactive protein. In this renewal, we propose: 1) to continue the development of our high successful variation discovery resource by examining 300 additional candidate genes involved in inflammation as well as other biological systems and pathways important to heart, lung, blood, and sleep disease phenotypes as requested by NHLBI investigators; 2) to enhance the information associated with large-scale variation datasets in SeattleSNPs, the PGAs and dbSNP for NHLBI investigators using in silico Iunctional predictions and population genetic analyses; 3) to model and explore key questions in population genetic within the PGA resources and to explore hypothesis by exploring variation in additional human populations and as requested by NHLBI investigators; 4) to increase our collaborative efforts in helping NHLBI investigators apply variation resources in large-scale association studies explore disease susceptibility and resistance in human populations; and 5) to continue educational opportunities on genetic analysis and population genetic of human populations through tutorials offered by the PGAs, and through hands-on computational intensive workshops offered in Seattle. Therefore, our plan to generate new resources and work with the NHLBI investigators to explore the relationships that exist between variations in human genes, and variation in risk for common disorders influencing human heart, lung or blood function.